Nanotechnology-mediated Drug Delivery through Tunnelling Nanotubes: A Critical Appraisal of Transport Mechanisms, Evidential Strength and Translational Constraints

Neha Jain *

Department of Biotechnology, Dronacharya Government College, Gurugram, Haryana, India.

Nikita Yadav

Department of Biotechnology, Dronacharya Government College, Gurugram, Haryana, India.

Anjali Bhakta

Department of Biotechnology, Dronacharya Government College, Gurugram, Haryana, India.

Pooja Kumari

Department of Biotechnology, Dronacharya Government College, Gurugram, Haryana, India.

*Author to whom correspondence should be addressed.


Abstract

Tunnelling nanotubes are thin, actin-supported membranous bridges that connect the cytoplasm of distant cells and carry vesicles, organelles, proteins and nucleic acids between them. Over the past two decades these structures have moved from a cell-biological curiosity to a candidate transport route for engineered nanocarriers, offering a conceptually distinct solution to the long-standing problem of poor penetration of therapeutics into dense, poorly vascularised tissue. This review examines critically whether the accumulated evidence supports the proposition that nanotube networks can be used deliberately and reliably as a drug-delivery pathway. Literature was identified through structured searching of biomedical and multidisciplinary scholarly sources, supplemented by backward and forward citation tracking, and appraised for methodological adequacy, attribution rigour and translational relevance rather than summarised study by study. Four findings dominate the synthesis. Transfer of diverse nanomaterials between cells along nanotube-like connections has been reported consistently across inorganic, carbon-based, lipid and polymeric carriers and across many cell types, yet the majority of observations rest on two-dimensional culture, short observation windows and morphological criteria that do not by themselves establish cytoplasmic continuity. Particle geometry, deformability and surface chemistry appear to govern transfer efficiency more strongly than particle size alone, although systematic comparative studies remain few. The same conduits that could distribute therapeutics also distribute resistance determinants, including functional mitochondria, efflux transporters and drug molecules themselves, which generates an unresolved contradiction between strategies seeking to suppress nanotube formation and strategies seeking to exploit it. Demonstration of nanotube-dependent delivery in living organisms remains sparse, and no quantitative framework exists for describing dose delivered through this route. The field currently supports mechanistic plausibility and proof of concept, but not claims of demonstrated therapeutic advantage. Priorities include standardised attribution criteria, quantitative in vivo imaging, context-specific rather than global modulation of nanotube formation, and explicit evaluation of the risk that engineered nanocarriers themselves induce the conduits they exploit.

Keywords: Tunnelling nanotubes, intercellular transport, nanoparticle drug delivery, tumour microenvironment, chemoresistance, mitochondrial transfer, translational nanomedicine


How to Cite

Jain, Neha, Nikita Yadav, Anjali Bhakta, and Pooja Kumari. 2026. “Nanotechnology-Mediated Drug Delivery through Tunnelling Nanotubes: A Critical Appraisal of Transport Mechanisms, Evidential Strength and Translational Constraints”. Journal of Basic and Applied Research International 32 (5):141-65. https://doi.org/10.56557/jobari/2026/v32i511168.

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